TY - JOUR
T1 - NKG2C is a major triggering receptor involved in the Vδ1 T cell-mediated cytotoxicity against HIV-infected CD4 T cells
AU - Fausther-Bovendo, Hugues
AU - Wauquier, Nadia
AU - Cherfils-Vicini, Julien
AU - Cremer, Isabelle
AU - Debré, Patrice
AU - Vieillard, Vincent
PY - 2008/1
Y1 - 2008/1
N2 - BACKGROUND: γδ T cells share with natural killer (NK) cells many effector capabilities and cell-surface proteins, including the NKG2 receptor family. A subset of γδ T cells that express the variable Vδ1 region plays a critical role in immune regulation, tumour surveillance and viral infection. Dramatic expansion of Vδ1 T cells has been observed in HIV disease. OBJECTIVE: To determine if NKG2C expression on Vδ1 T cells during HIV-1 infection is correlated with CD4 cell count and involved in lysis of CD4 T cells. METHODS: γδ T cells from viraemic HIV-infected patients were examined. Expression of NK cell markers was analyzed by flow cytometry. The cytolytic activity of Vδ1 T cells was determined by either Cr-release assays or degranulation assays against HLA-E-transfected 721.221 cells or HIV-infected CD4 primary T cells. RESULTS: The expression of C-type lectin NKG2 receptors was sharply modulated on γδ T cells in patients with HIV infection. A profound decrease of Vδ1 T cells bearing inhibitory NKG2A receptors corresponded to a drastic expansion of a distinct population of Vδ1 T cells expressing a functional activating NKG2C receptor. Engagement of HLA-E, the ligand of both NKG2A and NKG2C, which is specifically induced on HIV-infected CD4 T cells, substantially enhanced the Vδ1 T cell-mediated cytotoxicity. CONCLUSIONS: These results raise the possibility that induction of NKG2C expression on Vδ1 T cells plays a key role in the destruction of HIV-infected CD4 T cells during HIV disease.
AB - BACKGROUND: γδ T cells share with natural killer (NK) cells many effector capabilities and cell-surface proteins, including the NKG2 receptor family. A subset of γδ T cells that express the variable Vδ1 region plays a critical role in immune regulation, tumour surveillance and viral infection. Dramatic expansion of Vδ1 T cells has been observed in HIV disease. OBJECTIVE: To determine if NKG2C expression on Vδ1 T cells during HIV-1 infection is correlated with CD4 cell count and involved in lysis of CD4 T cells. METHODS: γδ T cells from viraemic HIV-infected patients were examined. Expression of NK cell markers was analyzed by flow cytometry. The cytolytic activity of Vδ1 T cells was determined by either Cr-release assays or degranulation assays against HLA-E-transfected 721.221 cells or HIV-infected CD4 primary T cells. RESULTS: The expression of C-type lectin NKG2 receptors was sharply modulated on γδ T cells in patients with HIV infection. A profound decrease of Vδ1 T cells bearing inhibitory NKG2A receptors corresponded to a drastic expansion of a distinct population of Vδ1 T cells expressing a functional activating NKG2C receptor. Engagement of HLA-E, the ligand of both NKG2A and NKG2C, which is specifically induced on HIV-infected CD4 T cells, substantially enhanced the Vδ1 T cell-mediated cytotoxicity. CONCLUSIONS: These results raise the possibility that induction of NKG2C expression on Vδ1 T cells plays a key role in the destruction of HIV-infected CD4 T cells during HIV disease.
KW - Cytotoxicity
KW - HIV-infected CD4 cells
KW - NKG2C receptor
KW - Vδ1 T cells
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U2 - 10.1097/QAD.0b013e3282f46e7c
DO - 10.1097/QAD.0b013e3282f46e7c
M3 - Article
C2 - 18097224
AN - SCOPUS:37549058389
SN - 0269-9370
VL - 22
SP - 217
EP - 226
JO - AIDS
JF - AIDS
IS - 2
ER -